1. Field of the Invention
This invention relates to the controlled release of medications or active substances which are administered transdermally. More particularly, this invention relates to a membrane for controlling the release of at least one drug or medication, which membrane can be fabricated or incorporated into a composite structure by heat sealing.
2. Description of the Prior Art
Rate controlling membranes have been used as a component of transdermal drug delivery devices. Silicone elastomers have often been employed in such applications because of the permeability of such elastomers to a number of drugs and medications. The use of silicone rubbers in such applications is limited commercially, however, because it is difficult to economically attach the cured membrane material to the other materials from which such devices are constructed. Such membranes are designed to control the rate at which these medications are released through the membrane into the skin of the patient. A reservoir containing the medication is sometimes placed between the membrane and an impermeable backing material, and a pressure sensitive adhesive applied over all or a portion of the membrane to attach the composite transdermal drug delivery device to the skin of the patient.
Depending upon the type of drug or medication and the desired release rate, the rate controlling portion of the device that is permeable to the medication has hithertofore been a layer of non-porous material such as ethylene vinyl acetate copolymer or crosslinked silicone rubber, or a porous film. The medication permeates through the matrix, if any, that forms the drug containing reservoir, the membrane, and the pressure sensitive adhesive, if the latter is positioned between the drug containing reservoir and the skin. The exposed surface of the pressure sensitive adhesive is generally covered by a release liner which is removed and discarded when the device is used.
A number of patents disclose the general concept of transdermal drug delivery devices. Representative of these is U.S. Pat. No. 3,598,122 to Zaffaroni. That patent discloses the use of silicone rubber as a membrane, but does not teach the use of the thermoplastic copolymers of the present invention.
In addition to lacking heat sealability, membranes of silicone rubber such as those disclosed in the prior art tend to be insufficiently permeable to provide the desired release rate of a medication particularly in the case of medications which are hydrophilic or of an ionic nature. Films and coatings formed from the hydrophobic silicone polymers are not preferred in such applications because of the limited permeability of such materials through the polymers which are generally of a hydrophobic nature. In some cases a matrix containing the drug to be administered is employed without a separate rate controlling membrane. Such embodiments are shown in U.S. Pat. No. 4,655,767 to Woodard et al.
U.S. Pat. No. 4,686,137, which issued to Ward and Riffle on Aug. 11, 1987, discloses the use as an additive in base polymers of small amounts of polyurethane urea-silicone block copolymers consisting essentially of a "hard" segment that is preferably a polyurethane formed from the reaction of diphenylmethane diisocyanate with a diol, and a "soft" segment having both hydrophilic and hydrophobic portions. The hydrophobic portion of the soft segment can be a polymeric tetraalkylene oxide, such as polytetramethylene oxide (PTMO), a polydialkylsiloxane, or a mixture of these two polymers, and the preferred hydrophilic segment is polyethylene oxide (PEO). These copolymers are combined with a base polymer, such as a polyurethane, and a suitable solvent to form films suitable for use as wound dressings or semipermeable membranes and as coating compositions for textile materials. As disclosed, however, the copolymers contain only a very minor weight percentage of silicone segments, and constitute only a small fraction of the weight of the base polymer, and thus would not be the equivalent of the polymers of this invention for use as a rate controlling membrane in a drug delivery device.
It has been reported that various copolymers of polysiloxanes can be used in drug delivery applications. See, for example, Ulman et al, Proceed. Intern. Symp. Control Rel. Bioact. Mater., 13: 228-229 (1986). However, even in light of these publications there has remained a need for a heat sealable membrane material which can be tailored to maximize the permeation therethrough of a wide variety of drugs.
An objective of this invention is to provide materials for membranes that enable the migration therethrough of a variety of medications and which can be heat sealed onto a variety of substrates or backings. By elimination of the need of using adhesives between the silicone membrane and other parts of the device (e.g. the backing), which adhesives might alter the rate of drug delivery or present either health hazards or problems of incompatability with the medication being administered, a number of problems encountered with the prior art are eliminated. Also an important advantage in the ability to employ commercially feasible assembly methods in manufacture of drug delivery devices is attained.